Cancer Research Targets Advances in Breast Cancer Research
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplementary Data
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by McCabe, N.
Right arrow Articles by Ashworth, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by McCabe, N.
Right arrow Articles by Ashworth, A.
[Cancer Research 66, 8109-8115, August 15, 2006]
© 2006 American Association for Cancer Research

Cell, Tumor, and Stem Cell Biology

Deficiency in the Repair of DNA Damage by Homologous Recombination and Sensitivity to Poly(ADP-Ribose) Polymerase Inhibition

Nuala McCabe1,2, Nicholas C. Turner2, Christopher J. Lord2, Katarzyna Kluzek3, Aneta Bialkowska3, Sally Swift1,2, Sabrina Giavara4, Mark J. O'Connor4, Andrew N. Tutt2, Malgorzata Z. Zdzienicka3,5, Graeme C.M. Smith4 and Alan Ashworth1,2

1 Cancer Research UK Gene Function and Regulation Group and 2 The Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London, United Kingdom; 3 Department of Molecular Cell Genetics, N. Copernicus University, Collegium Medicum in Bydgoszcz, Bydgoszcz, Poland; 4 KuDOS Pharmaceuticals Ltd., Cambridge, United Kingdom; and 5 Department of Toxicogenetics, Leiden University Medical Center, Leiden, the Netherlands

Requests for reprints: Alan Ashworth, The Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, Fulham Road, London SW3 6JB, United Kingdom. Phone: 44-20-7153-5317; Fax: 44-20-7153-5340; E-mail: alan.ashworth{at}icr.ac.uk.

Deficiency in either of the breast cancer susceptibility proteins BRCA1 or BRCA2 induces profound cellular sensitivity to the inhibition of poly(ADP-ribose) polymerase (PARP) activity. We hypothesized that the critical role of BRCA1 and BRCA2 in the repair of double-strand breaks by homologous recombination (HR) was the underlying reason for this sensitivity. Here, we examine the effects of deficiency of several proteins involved in HR on sensitivity to PARP inhibition. We show that deficiency of RAD51, RAD54, DSS1, RPA1, NBS1, ATR, ATM, CHK1, CHK2, FANCD2, FANCA, or FANCC induces such sensitivity. This suggests that BRCA-deficient cells are, at least in part, sensitive to PARP inhibition because of HR deficiency. These results indicate that PARP inhibition might be a useful therapeutic strategy not only for the treatment of BRCA mutation-associated tumors but also for the treatment of a wider range of tumors bearing a variety of deficiencies in the HR pathway or displaying properties of ‘BRCAness.’ (Cancer Res 2006; 66(16): 8109-15)




This article has been cited by other articles:


Home page
 JCBHome page
S. Badie, C. Liao, M. Thanasoula, P. Barber, M. A. Hill, and M. Tarsounas
RAD51C facilitates checkpoint signaling by promoting CHK2 phosphorylation
J. Cell Biol., May 18, 2009; 185(4): 587 - 600.
[Abstract] [Full Text] [PDF]

Home page
 haematolHome page
T. J. Gaymes, S. Shall, L. J. MacPherson, N. A. Twine, N. C. Lea, F. Farzaneh, and G. J. Mufti
Inhibitors of poly ADP-ribose polymerase (PARP) induce apoptosis of myeloid leukemic cells: potential for therapy of myeloid leukemia and myelodysplastic syndromes
Haematologica, May 1, 2009; 94(5): 638 - 646.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
T. Hay, J. R. Matthews, L. Pietzka, A. Lau, A. Cranston, A. O.H. Nygren, A. Douglas-Jones, G. C.M. Smith, N. M.B. Martin, M. O'Connor, et al.
Poly(ADP-Ribose) Polymerase-1 Inhibitor Treatment Regresses Autochthonous Brca2/p53-Mutant Mammary Tumors In vivo and Delays Tumor Relapse in Combination with Carboplatin
Cancer Res., May 1, 2009; 69(9): 3850 - 3855.
[Abstract] [Full Text] [PDF]

Home page
 Mol Cancer ResHome page
X. Hu, H. M. Stern, L. Ge, C. O'Brien, L. Haydu, C. D. Honchell, P. M. Haverty, B. A. Peters, T. D. Wu, L. C. Amler, et al.
Genetic Alterations and Oncogenic Pathways Associated with Breast Cancer Subtypes
Mol. Cancer Res., April 1, 2009; 7(4): 511 - 522.
[Abstract] [Full Text] [PDF]

Home page
 Ann OncolHome page
J. Fasano and F. Muggia
Breast cancer arising in a BRCA-mutated background: therapeutic implications from an animal model and drug development
Ann. Onc., April 1, 2009; 20(4): 609 - 614.
[Abstract] [Full Text] [PDF]

Home page
 J. Med. Genet.Home page
C Cybulski, B Gorski, T Huzarski, T Byrski, J Gronwald, T Debniak, D Wokolorczyk, A Jakubowska, P Serrano-Fernandez, T Dork, et al.
Effect of CHEK2 missense variant I157T on the risk of breast cancer in carriers of other CHEK2 or BRCA1 mutations
J. Med. Genet., February 1, 2009; 46(2): 132 - 135.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Prevention ResearchHome page
J. E. Garber
BRCA1/2-Associated and Sporadic Breast Cancers: Fellow Travelers or Not?
Cancer Prevention Research, February 1, 2009; 2(2): 100 - 103.
[Full Text] [PDF]

Home page
 Cancer Res.Home page
A. Ashworth
Drug Resistance Caused by Reversion Mutation
Cancer Res., December 15, 2008; 68(24): 10021 - 10023.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
O. I. Olopade, T. A. Grushko, R. Nanda, and D. Huo
Advances in Breast Cancer: Pathways to Personalized Medicine
Clin. Cancer Res., December 15, 2008; 14(24): 7988 - 7999.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
B. P. Schneider, E. P. Winer, W. D. Foulkes, J. Garber, C. M. Perou, A. Richardson, G. W. Sledge, and L. A. Carey
Triple-Negative Breast Cancer: Risk Factors to Potential Targets
Clin. Cancer Res., December 15, 2008; 14(24): 8010 - 8018.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Pathol.Home page
D S P Tan, C Marchio, and J S Reis-Filho
Hereditary breast cancer: from molecular pathology to tailored therapies
J. Clin. Pathol., October 1, 2008; 61(10): 1073 - 1082.
[Abstract] [Full Text] [PDF]

Home page
 Br. J. Radiol.Home page
C Jones and E R Plummer
PARP inhibitors and cancer therapy -- early results and potential applications
Br. J. Radiol., October 1, 2008; 81(Special_Issue_1): S2 - S5.
[Abstract] [Full Text] [PDF]

Home page
 Br. J. Radiol.Home page
S Kyle, H D Thomas, J Mitchell, and N J Curtin
Exploiting the Achilles heel of cancer: the therapeutic potential of poly(ADP-ribose) polymerase inhibitors in BRCA2-defective cancer
Br. J. Radiol., October 1, 2008; 81(Special_Issue_1): S6 - S11.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
H. T. Lynch, J. N. Marcus, and W. S. Rubinstein
Stemming the Tide of Cancer for BRCA1/2 Mutation Carriers
J. Clin. Oncol., September 10, 2008; 26(26): 4239 - 4243.
[Full Text] [PDF]

Home page
 JCOHome page
A. Ashworth
A Synthetic Lethal Therapeutic Approach: Poly(ADP) Ribose Polymerase Inhibitors for the Treatment of Cancers Deficient in DNA Double-Strand Break Repair
J. Clin. Oncol., August 1, 2008; 26(22): 3785 - 3790.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
J. N. Sarkaria, G. J. Kitange, C. D. James, R. Plummer, H. Calvert, M. Weller, and W. Wick
Mechanisms of Chemoresistance to Alkylating Agents in Malignant Glioma
Clin. Cancer Res., May 15, 2008; 14(10): 2900 - 2908.
[Abstract] [Full Text] [PDF]

Home page
 aacredbookHome page
E. R. Plummer and H. Calvert
Targeting Poly(ADP-Ribose) Polymerase: A Two-Armed Strategy for Cancer Therapy
Am. Assoc. Cancer Res. Educ. Book, April 12, 2008; 2008(1): 15 - 22.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J.-F. Haince, D. McDonald, A. Rodrigue, U. Dery, J.-Y. Masson, M. J. Hendzel, and G. G. Poirier
PARP1-dependent Kinetics of Recruitment of MRE11 and NBS1 Proteins to Multiple DNA Damage Sites
J. Biol. Chem., January 11, 2008; 283(2): 1197 - 1208.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
S. Adimoolam, M. Sirisawad, J. Chen, P. Thiemann, J. M. Ford, and J. J. Buggy
HDAC inhibitor PCI-24781 decreases RAD51 expression and inhibits homologous recombination
PNAS, December 4, 2007; 104(49): 19482 - 19487.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
S. Beneke and A. Burkle
Poly(ADP-ribosyl)ation in mammalian ageing
Nucleic Acids Res., December 3, 2007; 35(22): 7456 - 7465.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
E. R. Plummer and H. Calvert
Targeting Poly(ADP-Ribose) Polymerase: A Two-Armed Strategy for Cancer Therapy
Clin. Cancer Res., November 1, 2007; 13(21): 6252 - 6256.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J.-F. Haince, S. Kozlov, V. L. Dawson, T. M. Dawson, M. J. Hendzel, M. F. Lavin, and G. G. Poirier
Ataxia Telangiectasia Mutated (ATM) Signaling Network Is Modulated by a Novel Poly(ADP-ribose)-dependent Pathway in the Early Response to DNA-damaging Agents
J. Biol. Chem., June 1, 2007; 282(22): 16441 - 16453.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
C. K. Donawho, Y. Luo, Y. Luo, T. D. Penning, J. L. Bauch, J. J. Bouska, V. D. Bontcheva-Diaz, B. F. Cox, T. L. DeWeese, L. E. Dillehay, et al.
ABT-888, an Orally Active Poly(ADP-Ribose) Polymerase Inhibitor that Potentiates DNA-Damaging Agents in Preclinical Tumor Models
Clin. Cancer Res., May 1, 2007; 13(9): 2728 - 2737.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2006 by the American Association for Cancer Research.